ADRO_RAT
ID ADRO_RAT Reviewed; 494 AA.
AC P56522;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 15-JUL-1998, sequence version 1.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=NADPH:adrenodoxin oxidoreductase, mitochondrial;
DE Short=AR;
DE Short=Adrenodoxin reductase;
DE EC=1.18.1.6 {ECO:0000269|PubMed:10525147};
DE AltName: Full=Ferredoxin--NADP(+) reductase;
DE Short=Ferredoxin reductase;
DE Flags: Precursor;
GN Name=Fdxr;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 35-54, FUNCTION, CATALYTIC
RP ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RC STRAIN=Wistar; TISSUE=Adrenal gland;
RX PubMed=10525147; DOI=10.1016/s0167-4838(99)00180-6;
RA Sagara Y., Watanabe Y., Kodama H., Aramaki H.;
RT "cDNA cloning, overproduction and characterization of rat adrenodoxin
RT reductase.";
RL Biochim. Biophys. Acta 1434:284-295(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Ovary;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP SUBCELLULAR LOCATION.
RX PubMed=2170421; DOI=10.1083/jcb.111.4.1373;
RA Hanukoglu I., Suh B.S., Himmelhoch S., Amsterdam A.;
RT "Induction and mitochondrial localization of cytochrome P450scc system
RT enzymes in normal and transformed ovarian granulosa cells.";
RL J. Cell Biol. 111:1373-1381(1990).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=16641100; DOI=10.1073/pnas.0600895103;
RA Hoffert J.D., Pisitkun T., Wang G., Shen R.-F., Knepper M.A.;
RT "Quantitative phosphoproteomics of vasopressin-sensitive renal cells:
RT regulation of aquaporin-2 phosphorylation at two sites.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:7159-7164(2006).
CC -!- FUNCTION: Serves as the first electron transfer protein in all the
CC mitochondrial P450 systems including cholesterol side chain cleavage in
CC all steroidogenic tissues, steroid 11-beta hydroxylation in the adrenal
CC cortex, 25-OH-vitamin D3-24 hydroxylation in the kidney, and sterol C-
CC 27 hydroxylation in the liver. {ECO:0000269|PubMed:10525147}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + NADP(+) + 2 reduced [adrenodoxin] = NADPH + 2 oxidized
CC [adrenodoxin]; Xref=Rhea:RHEA:42312, Rhea:RHEA-COMP:9998, Rhea:RHEA-
CC COMP:9999, ChEBI:CHEBI:15378, ChEBI:CHEBI:33737, ChEBI:CHEBI:33738,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.18.1.6;
CC Evidence={ECO:0000269|PubMed:10525147};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:P08165};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.32 uM for NADPH {ECO:0000269|PubMed:10525147};
CC -!- PATHWAY: Steroid metabolism; cholesterol metabolism.
CC {ECO:0000269|PubMed:10525147}.
CC -!- SUBUNIT: Monomer. Interacts directly with FDX1.
CC {ECO:0000250|UniProtKB:P08165}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000269|PubMed:2170421}; Peripheral membrane protein
CC {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the ferredoxin--NADP reductase type 1 family.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; D63761; BAA23759.1; -; mRNA.
DR EMBL; BC088844; AAH88844.1; -; mRNA.
DR RefSeq; NP_077067.1; NM_024153.1.
DR AlphaFoldDB; P56522; -.
DR SMR; P56522; -.
DR IntAct; P56522; 2.
DR STRING; 10116.ENSRNOP00000004592; -.
DR iPTMnet; P56522; -.
DR PhosphoSitePlus; P56522; -.
DR jPOST; P56522; -.
DR PaxDb; P56522; -.
DR PRIDE; P56522; -.
DR Ensembl; ENSRNOT00000085636; ENSRNOP00000075248; ENSRNOG00000058497.
DR GeneID; 79122; -.
DR KEGG; rno:79122; -.
DR CTD; 2232; -.
DR RGD; 621648; Fdxr.
DR eggNOG; KOG1800; Eukaryota.
DR GeneTree; ENSGT00940000165377; -.
DR HOGENOM; CLU_024722_3_1_1; -.
DR InParanoid; P56522; -.
DR OMA; RFNFIGN; -.
DR OrthoDB; 1324510at2759; -.
DR PhylomeDB; P56522; -.
DR BioCyc; MetaCyc:MON-14306; -.
DR Reactome; R-RNO-196108; Pregnenolone biosynthesis.
DR Reactome; R-RNO-211976; Endogenous sterols.
DR Reactome; R-RNO-2395516; Electron transport from NADPH to Ferredoxin.
DR UniPathway; UPA00296; -.
DR PRO; PR:P56522; -.
DR Proteomes; UP000002494; Chromosome 10.
DR Bgee; ENSRNOG00000058497; Expressed in ovary and 19 other tissues.
DR Genevisible; P56522; RN.
DR GO; GO:0005743; C:mitochondrial inner membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0070402; F:NADPH binding; IDA:RGD.
DR GO; GO:0015039; F:NADPH-adrenodoxin reductase activity; IDA:RGD.
DR GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR GO; GO:0008203; P:cholesterol metabolic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0070995; P:NADPH oxidation; IDA:RGD.
DR GO; GO:0006744; P:ubiquinone biosynthetic process; IBA:GO_Central.
DR Gene3D; 3.50.50.60; -; 1.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR InterPro; IPR023753; FAD/NAD-binding_dom.
DR InterPro; IPR021163; Ferredox_Rdtase_adrenod.
DR Pfam; PF07992; Pyr_redox_2; 1.
DR PIRSF; PIRSF000362; FNR; 1.
DR SUPFAM; SSF51905; SSF51905; 1.
PE 1: Evidence at protein level;
KW Cholesterol metabolism; Direct protein sequencing; Electron transport; FAD;
KW Flavoprotein; Lipid metabolism; Membrane; Mitochondrion;
KW Mitochondrion inner membrane; NADP; Oxidoreductase; Phosphoprotein;
KW Reference proteome; Steroid metabolism; Sterol metabolism; Transit peptide;
KW Transport.
FT TRANSIT 1..34
FT /note="Mitochondrion"
FT /evidence="ECO:0000269|PubMed:10525147"
FT CHAIN 35..494
FT /note="NADPH:adrenodoxin oxidoreductase, mitochondrial"
FT /id="PRO_0000019422"
FT BINDING 51
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P08165"
FT BINDING 72
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P08165"
FT BINDING 80
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P08165"
FT BINDING 116
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P08165"
FT BINDING 187..190
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P08165"
FT BINDING 231..232
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P08165"
FT BINDING 243
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P08165"
FT BINDING 401
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P08165"
FT BINDING 408..410
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P08165"
FT BINDING 408
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P08165"
FT MOD_RES 313
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P22570"
SQ SEQUENCE 494 AA; 54363 MW; 5F07B37DFAA9525D CRC64;
MAPRCWRWWS WSAWPGVRPL PSRSTPTPGF CKKFSTQETT PQICVVGSGP AGFYTAQHLL
KHHTRAHVDI YEKQLVPFGL VRFGVAPDHP EVKNVINTFT QTARSDRCAF RGNVVVGRDV
SVPELREAYH AVVLSYGAED HQPLEIPGEE LPGVVSARAF VGWYNGLPEN QKLAPDLSCD
TAVILGQGNV ALDVARILLT PPEHLEKTDI TEVALGVLRQ SRVKTVWIVG RRGPLQVAFT
IKELREMIQL PGTQPILDPS DFLGLQDRIK DVPRPRKRLT ELLLRTATEK PGVEEAARRA
LASRAWGLRF FRSPQQVLPT PDGRRVAGIR LAVTRLEGVG ESTRAVPTGD VEDLPCGLLL
SSVGYKSRPI DPSVPFDPKL GIIPNTEGRV VNAPGLYCSG WVKRGPTGVI TTTMTDSFLT
SQVLLKDLKA GLLPSGPRPG YTAIQALLSD RGVRPVSFSD WEKLDAEEVA RGQGTGKPRE
KLVDRREMLQ LLGH
